Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) incidentally diagnosed after lung surgery: analysis of a large cohort of consecutive patients

<bold>Introduction:</bold> DIPNECH is a rare and under-recognized pre-neoplastic condition, often incidentally found on surgical specimen. <bold>Aims:</bold> We sought to identify predictive factors for DIPNECH, focusing on clinico-pathological and radiological characteristics. <bold>Methods:</bold> Data of a single-center cohort of patients undergoing lung resection with DIPNECH diagnosis on surgical specimens were retrospectively analyzed. Pre-operative computed tomography (CT) images were reviewed to identify radiological-pathological correlation. <bold>Results:</bold> Among 2340 patients surgically treated from January 2016 to December 2023, twenty-six had incidental histological finding of DIPNECH (F/M: 22/4; 69.4±9.4 years; 30.8% never-smokers; 11.5% asthma; 50% cough). Surgery consisted of 38.4% lobectomies, 15.4% segmentectomies and 46.2% wedge resections. There were 30.8% benign lesions and 69.2% malignant: 13 carcinoids, 4 adenocarcinomas and 1 ovarian cancer metastasis. Pathologic exam revealed at least one tumorlet in 65.4% patients. Review of pre-operative chest-CT showed bilateral small nodules suggestive of DIPNECH in 80.8% patients and the incidental histologically found lesions were identified in 53.9%. The presence of ≥1 tumorlets in lung specimen was significantly associated with diffuse micronodules on CT-scan (OR 0.119, 95% CI: 0.018-0.785; p=0.027). <bold>Conclusions:</bold> Radiological finding of multiple small, scattered nodules associated with a dominant lung lesion may be predictive for DIPNECH. Incidental pre-cancerous lesions in patients with benign lung disease suggest the need for follow-up protocols, although further studies are needed to advance DIPNECH knowledge.